A Clinical Trial of HRS5580 for Injection Combined With Palonosetron Hydrochloride for the Prevention of Postoperative Nausea and Vomiting

Inclusion criteria

• Voluntarily sign the informed consent form prior to the start of any trial-related activities, fully understand the purpose and significance of the study, and voluntarily comply with the trial procedures;
• 2、Scheduled to undergo elective surgery under general anesthesia with an expected surgical duration of ≥ 2 hours (surgery types include gynecological surgery, hepatobiliary surgery, intestinal surgery, urological surgery, etc.);
• Aged ≥ 18 years;
• Body Mass Index (BMI) between 18 kg/m² and 28 kg/m² (inclusive);
• American Society of Anesthesiologists (ASA) Physical Status Classification I or II;
• Expected postoperative hospital stay ≥ 72 hours;
• Presence of ≥ 3 risk factors for PONV (female, history of PONV or motion sickness, non-smoker, postoperative opioid use);
• Female participants of childbearing potential must have a negative serum pregnancy test within 7 days prior to randomization and must not be breastfeeding; female participants of childbearing potential must use highly effective contraceptive measures (see Appendix 13.1.2) from 30 days prior to the screening period until 6 months after the last dose, and have no plans for egg donation or pregnancy; male participants with a female partner of childbearing potential must use highly effective contraceptive measures from the time of signing the informed consent form until 6 months after the last dose.

Exclusion criteria

• Patients with a history of vestibular disorders (including but not limited to: peripheral vestibular syndrome, central vestibular syndrome, etc.) or dizziness (excluding history of motion sickness), or a history of central nervous system disorders that may cause nausea and vomiting;
• History of chronic nausea or vomiting/retching;
• History of new-onset myocardial infarction or unstable angina pectoris within 6 months prior to screening, or history of severe cardiac arrhythmias such as second-degree or higher atrioventricular block, or history of New York Heart Association (NYHA) Functional Classification Class II or higher;
• Any other medical condition that, in the investigator's judgment, may confound the assessment of postoperative nausea and/or vomiting.
• Random blood glucose > 11.1 mmol/L during the screening period;
• Prolonged QTc interval during the screening period: > 450 ms in males, > 470 ms in females;
• Systolic blood pressure ≥ 160 mmHg or < 90 mmHg, and/or diastolic blood pressure ≥ 100 mmHg or < 60 mmHg from the time of signing the ICF to before entering the operating room, which is considered clinically significant by the investigator;
• Abnormal liver function during the screening period: aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) and/or gamma-glutamyl transferase (GGT) ≥ 3.0 × ULN and/or total bilirubin (TBIL) ≥ 1.5 × ULN;
• Abnormal renal function during the screening period: serum creatinine (Cr) ≥ 1.5 × ULN and/or participants undergoing dialysis;
• Positive test for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCVAb), syphilis antibody, or human immunodeficiency virus (HIV) antibody during the screening period;
• Known allergy or contraindication to NK-1 receptor antagonists and/or 5-HT3 receptor antagonists and other medications that may be used during the trial;
• Receipt of any treatment with potential antiemetic effects, including pharmacological and non-pharmacological treatments, within 48 hours prior to the start of investigational product administration (refer to the Prohibited Concomitant Treatments table);
• Participants whose last use of an opioid occurred less than 5 half-lives before the start of investigational product administration;
• Use of strong CYP3A4 inducers, strong inhibitors, or specific CYP2D6 substrates within 28 days prior to randomization.
• Participants who have received chemotherapy within 4 weeks prior to surgery;
• Use of other medications that may affect antiemetic efficacy as determined by the investigator, with the last use occurring less than 5 half-lives before the start of investigational product administration (based on the actual drug label; if the half-life is unknown, a 48-hour washout period should be applied).
• Participants scheduled to receive anesthetic methods not specified in the protocol, including local anesthesia, regional anesthesia [e.g., nerve block, neuraxial block (including subarachnoid block, epidural anesthesia, or combined spinal-epidural anesthesia)], and total intravenous anesthesia;
• Participants expected to require an in-place nasogastric tube or orogastric tube after surgery completion;
• Participants expected to be transferred to the ICU for sedation with endotracheal intubation after surgery or those unable to undergo nausea and vomiting record assessments;
• Participation in another clinical study of a drug or device within 3 months prior to screening (having signed informed consent and received investigational product/device treatment);
• Daily excessive consumption of tea, coffee, grapefruit/grapefruit juice, pomelo juice, or caffeinated beverages (average > 8 cups per day, 200 mL per cup) within 14 days prior to randomization;
• Any other condition that, in the investigator's opinion, makes the participant unsuitable for participation in this trial.